(6R-trans)-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione (tadalafil) having the formula

is a potent and selective inhibitor of the cyclic guanosine monophosphate (cGMP)—specific phosphodiesterase enzyme PDE5. The inhibition of PDE5 increases the amount of cGMP, resulting in smooth muscle relaxation and increased blood flow. Tadalafil is therefore currently used in the treatment of male erectile dysfunction.
The solid state physical properties of an active pharmaceutical ingredient (API), such as tadalafil, can be very important in formulating a drug substance and can have profound effects on the ease and reproducibility of formulation. Particle size, for example, may effect the flowability and mixability of a drug substance. Small particles are also filtered and washed more slowly during isolation processes, and thus may increase the time and expense of manufacturing a drug formulation.
U.S. Pat. No. 5,859,006 discloses the synthesis of tadalafil. U.S. Pat. No. 6,821,975 describes the synthesis of tadalafil wherein 90% of the particles have a particle size of less than about 40 microns and a pharmaceutical composition containing this particle size.
There is a need in the art for tadalafil having a large particle size and for a process for the preparation thereof.